Sweeney M F, Hasan N, Soto A M, Sonnenschein C
Program in Genetics, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, 02111, USA.
Program in Cell, Molecular & Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, 02111, USA.
Rev Endocr Metab Disord. 2015 Dec;16(4):341-57. doi: 10.1007/s11154-016-9337-4.
Incidences of altered development and neoplasia of male reproductive organs have increased during the last 50 years, as shown by epidemiological data. These data are associated with the increased presence of environmental chemicals, specifically "endocrine disruptors," that interfere with normal hormonal action. Much research has gone into testing the effects of specific endocrine disrupting chemicals (EDCs) on the development of male reproductive organs and endocrine-related cancers in both in vitro and in vivo models. Efforts have been made to bridge the accruing laboratory findings with the epidemiological data to draw conclusions regarding the relationship between EDCs, altered development and carcinogenesis. The ability of EDCs to predispose target fetal and adult tissues to neoplastic transformation is best explained under the framework of the tissue organization field theory of carcinogenesis (TOFT), which posits that carcinogenesis is development gone awry. Here, we focus on the available evidence, from both empirical and epidemiological studies, regarding the effects of EDCs on male reproductive development and carcinogenesis of endocrine target tissues. We also critique current research methodology utilized in the investigation of EDCs effects and outline what could possibly be done to address these obstacles moving forward.
流行病学数据显示,在过去50年中,男性生殖器官发育改变和肿瘤形成的发生率有所增加。这些数据与环境化学物质尤其是“内分泌干扰物”的增加有关,这些物质会干扰正常的激素作用。许多研究致力于测试特定内分泌干扰化学物质(EDCs)在体外和体内模型中对男性生殖器官发育和内分泌相关癌症的影响。人们已努力将不断积累的实验室研究结果与流行病学数据相结合,以得出关于EDCs、发育改变和致癌作用之间关系的结论。在致癌作用的组织组织场理论(TOFT)框架下,能最好地解释EDCs使靶胎儿和成人组织易发生肿瘤转化的能力,该理论认为致癌作用是发育出现偏差。在此,我们关注来自实证研究和流行病学研究的现有证据,这些证据涉及EDCs对男性生殖发育和内分泌靶组织致癌作用的影响。我们还对当前用于研究EDCs影响的研究方法进行了批判,并概述了为克服这些障碍未来可能采取的措施。